DRUG-INDUCED DNA-REPAIR - X-RAY STRUCTURE OF A DNA-DITERCALINIUM COMPLEX

被引：76

作者：

GAO, Q ^{[1
]}

WILLIAMS, LD ^{[1
]}

EGLI, M ^{[1
]}

RABINOVICH, D ^{[1
]}

CHEN, SL ^{[1
]}

QUIGLEY, GJ ^{[1
]}

RICH, A ^{[1
]}

机构：

[1] CUNY HUNTER COLL,NEW YORK,NY 10021

来源：

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA | 1991年 / 88卷 / 06期

关键词：

D O I：

10.1073/pnas.88.6.2422

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

Ditercalinium is a synthetic anticancer drug that binds to DNA by bis-intercalation and activates DNA repair processes. In prokaryotes, noncovalent DNA-ditercalinium complexes are incorrectly recognized by the uvrABC repair system as covalent lesions on DNA. In eukaryotes, mitochondrial DNA is degraded by excess and futile DNA repair. Using x-ray crystallography, we have determined, to 1.7 angstrom resolution, the three-dimensional structure of a complex of ditercalinium bound to the double-stranded DNA fragment [d(CGCG)]2. The DNA in the complex with ditercalinium is kinked (by 15-degrees) and severely unwound (by 36-degrees) with exceptionally wide major and minor grooves. Recognition of the DNA-ditercalinium complex by uvrABC in prokaryotes, and by mitochondrial DNA repair systems in eukaryotes, might be related to drug-induced distortion of the DNA helix.

引用

页码：2422 / 2426

页数：5

共 27 条

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